A novel network-based method identifies a cuproplasia-related pan-cancer gene signature to predict patient outcome

IF 3.8 2区 生物学 Q2 GENETICS & HEREDITY Human Genetics Pub Date : 2024-04-20 DOI:10.1007/s00439-024-02673-2
Vu Viet Hoang Pham, Toni Rose Jue, Jessica Lilian Bell, Fabio Luciani, Filip Michniewicz, Giuseppe Cirillo, Linda Vahdat, Chelsea Mayoh, Orazio Vittorio
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Abstract

Copper is a vital micronutrient involved in many biological processes and is an essential component of tumour cell growth and migration. Copper influences tumour growth through a process called cuproplasia, defined as abnormal copper-dependent cell-growth and proliferation. Copper-chelation therapy targeting this process has demonstrated efficacy in several clinical trials against cancer. While the molecular pathways associated with cuproplasia are partially known, genetic heterogeneity across different cancer types has limited the understanding of how cuproplasia impacts patient survival. Utilising RNA-sequencing data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets, we generated gene regulatory networks to identify the critical cuproplasia-related genes across 23 different cancer types. From this, we identified a novel 8-gene cuproplasia-related gene signature associated with pan-cancer survival, and a 6-gene prognostic risk score model in low grade glioma. These findings highlight the use of gene regulatory networks to identify cuproplasia-related gene signatures that could be used to generate risk score models. This can potentially identify patients who could benefit from copper-chelation therapy and identifies novel targeted therapeutic strategies.

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一种基于网络的新方法可确定与杯状增生症相关的泛癌基因特征,从而预测患者的预后
铜是一种重要的微量营养元素,参与许多生物过程,是肿瘤细胞生长和迁移的重要组成部分。铜通过一种称为 "铜增生 "的过程影响肿瘤的生长。"铜增生 "是指依赖铜的细胞异常生长和增殖。针对这一过程的铜螯合疗法已在多项抗癌临床试验中显示出疗效。虽然与铜增生相关的分子途径已部分清楚,但不同癌症类型的遗传异质性限制了人们对铜增生如何影响患者生存的了解。利用癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据集的 RNA 测序数据,我们生成了基因调控网络,以确定 23 种不同癌症类型中与杯状增生症相关的关键基因。由此,我们确定了与泛癌症生存相关的新型 8 基因杯状增生相关基因特征,以及低级别胶质瘤的 6 基因预后风险评分模型。这些发现强调了利用基因调控网络确定杯状增生相关基因特征的重要性,这些特征可用于生成风险评分模型。这有可能确定哪些患者可以从铜螯合疗法中获益,并确定新的靶向治疗策略。
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来源期刊
Human Genetics
Human Genetics 生物-遗传学
CiteScore
10.80
自引率
3.80%
发文量
94
审稿时长
1 months
期刊介绍: Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.
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